ANALYSIS OF A SEQUENCED CDNA LIBRARY FROM MULTIPLE-SCLEROSIS LESIONS

To identify genes that are expressed in MS pathogenesis, we have analy zed a normalized cDNA library made from mRNA obtained from CNS lesions of a patient with primary progressive MS. Complementary DNA clones ob tained from this library were subjected to automated DNA sequencing to generate expressed sequence tags. Analysis of this MS cDNA library re vealed the presence of 54 cDNAs that were associated with immune activ ation and indicated the presence of an ongoing inflammatory response w ith evidence of both cell-mediated and humoral immune responses. The s urprising finding was that 16 of the cDNAs encoded autoantigens associ ated with seven other autoimmune disorders, while only three of these 16 autoantigen cDNAs were present in a similarly constructed adult bra in library. Such aberrant autoantigen expression could provide a sourc e of secondary autoimmune stimulation that could contribute to the ong oing inflammatory response in MS. In addition, two cDNAs were found th at mapped to a known MS susceptibility locus (5p14-p12): one encoded a n excitatory amino acid transporter and the other a human homologue of the Drosophila disabled gene. This approach to the molecular biology of MS pathogenesis may help to illuminate previously unappreciated asp ects of this disease.